Scientists publish new research using data from the 100,000 Genomes Project rare disease programme

Scientists from the University of Cambridge have announced a discovery about the inheritance of mitochondrial DNA using data from the 100,000 Genomes Project. The scientists are part of the neurology domain of the Genomics England Clinical Interpretation Partnership (GeCIP). These important scientific findings represent the beginning of a stream of valuable discoveries that will come from the 100,000 Genomes Project data.

The research has been published in the journal, Science. We asked study authors Professor Patrick Chinnery, Dr Ernest Turro, and Dr Wei Wei about their research.

What do we mean by ‘mitochondrial DNA’?

Mitochondria, the ‘powerhouses’ inside cells that produce energy, have their own DNA called mitochondrial DNA. This is distinct from so-called ‘nuclear DNA’, which is contained in the cell’s nucleus and determines most of a person’s characteristics. Our nuclear DNA comes from both our mother and father, but our mitochondrial DNA only comes from our mother. Each cell can contain hundreds of mitochondria.

Nuclear DNA and mitochondrial DNA can change – these changes are called mutations. However, not all of the hundreds of mitochondria in a cell will have the same mutations. Having a mixture of normal and mutated mitochondrial DNA is called ‘heteroplasmy’.

In our study, we investigated how mitochondrial DNA mutations and heteroplasmies change when they are passed from a mother to her child. We found that 45% of people carry at least one mutation that affects more than 1% of their mitochondrial DNA. The proportion of mitochondrial DNA that carries a particular mutation can change when mitochondria are passed from mother to child. For some, the percentage level of heteroplasmy increases, and for others it decreases. This shapes mitochondrial DNA in the human population.

We also found that, for approximately 1 in 40 people in our UK-based study, their mitochondrial DNA originates from a different geographical population than their nuclear DNA. In these individuals, new mutations in their mitochondrial DNA are more likely to match the geographic origins of the nuclear DNA than the geographic origins of the mitochondrial DNA. This suggests that the nucleus is ‘shaping’ our mitochondrial DNA when it is passed from mother to child.

Do these findings have implications for patients or the public?

Although there are no immediate implications for patients or the public, our work gives the first clue that our cell nucleus ‘prefers’ some kinds of mitochondrial DNA. This might be important when carrying our ‘mitochondrial transfer’ to help prevent the inheritance of severe mitochondrial diseases.

Mitochondrial transfer is an in vitro fertilisation (IVF) technique for preventing inherited mitochondrial diseases. It involves taking the DNA out of a woman’s egg or embryo that has faulty mitochondria and transferring it to a donor egg or embryo with healthy mitochondria.

Matching both the mitochondrial background and the nuclear background of the donor could be important when selecting potential mitochondrial donors, although further work is needed to show whether this will be important in the long term.

Dr Freya Boardman-Pretty from the Genomics England Clinical Interpretation Partnership (GeCIP) team, explains how the GeCIP helps to enable important research like this to happen.

How does being involved with the GeCIP help scientists to carry out important research?

The GeCIP (Genomics England Clinical Interpretation Partnership) is a community of researchers and clinicians from academia and healthcare, who are based in the UK and worldwide. This community uses the 100,000 Genomes Project data to improve our understanding of genomics and health.

The Project dataset is an incredibly rich and unique resource. As well as the 100,000 whole genomes from participants, it also includes detailed clinical data such as linked longitudinal health records from the NHS. Access to this detailed and comprehensive information helps scientists and clinicians to answer questions about health that we have not been able to answer before.

How does the work of the GeCIP community help patients?

One important aim of the GeCIP is to use the community’s expertise to find diagnoses for the 100,000 Genomes Project participants where our interpretation pipeline has not found a possible cause of their disease. This means Genomics England can feedback additional diagnoses to individual patients and improve the way results are interpreted in the future.

GeCIP includes many diverse research areas, called “domains”. Scientists studying rare diseases often look for novel genes that might play a part in how a disease develops and progresses. Cancer researchers aim to identify new mutations that might promote the development of cancer, or use genetic and clinical data to study how cancers change when patients undergo treatments.

Identifying relevant genes in disease can open up new avenues of research, and help us to find new treatment options for patients.

Members of the GeCIP apply to join wanting to answer specific questions, but we also expect them to contribute to wider knowledge across the Project, such as adding expert reviews to PanelAppor helping to train new GeCIP members.

One of the main principles of the GeCIP is that research should be collaborative rather than competitive. Ongoing research is registered so that other GeCIP members can find projects that they might like to work on with other scientists. Hopefully, this avoids duplicating research efforts and ultimately leads to better scientific results.

The GeCIP is constantly growing, with numerous applications to join every week. Individuals can apply to join here.

You can read more about this study on the University of Cambridge website